Drug delivery routes commonly comprise oral administration, inhalation, sublingual administration, external application, rectal administration, and injection, etc.
Since drugs can be absorbed into blood directly through the mucosa of mouth or nose after being inhaled orally or nasally, it can bypass the first-pass effect of the liver. The method of inhalation through mouth or nose is a most quick and effective way for the treatment of many diseases, of which asthma is the most common disease.
Nowadays, available devices of inhalation for the treatment of respiratory diseases such as asthma mainly include two types, the pressurized metered-dose inhalation device and the dry powder inhalation device.
For the aerosol-dosing device, with the improvement of environmental awareness both at home and abroad, chlorofluorocarbon (CFC) aerosols have been eliminated gradually. Chlorofluorocarbon, a haloalkane consisting of chlorine, fluorine and carbon, was used as a refrigerant in refrigerators at first, but its production was prohibited officially since 1 Jan. 1996 for its decomposition of the ozone layer. It is open for the study of new desirable aerosols.
On the other hand, if a pressurized metered-dose inhalation device is used, the user must coordinate the rhythm of spraying and inhalation well so as to obtain desirable drug inhalation effects.
The dry powder inhalation device is breath actuated, and there is no problem of rhythm coordination of spraying and inhalation.
Based on the type of drug storage, the dry powder inhalation device is divided into two types, isolated packages and one reservoir.
1). Dry Powder Inhalation Device with Isolated Packages:
Taking the commercially available Seretide accuhaler for instance, an inhalator described in a Chinese patent (Notice of Announcement No. CN 1313171C, Date of Announcement May 2, 2007) comprises a plurality of isolated cavities each of which contains a drug in a metered amount, and a lever which makes the cavities move one by one to align with the inhalation hole, wherein each cavity comprises an internal flange and an external rim, and said cavities are closed by sealing layers. The inhalator also comprises a mechanism for lifting the sealing layer away from the internal flange and external rim of the cavity so as to open the air passage formed by the cavity and the sealing layer. Therefore, when the user inhales from the pipe orifice, the drug powder in the cavity is carried by the air in the flow passage and taken out from the pipe orifice of the inhalator.
It is found in use that this type of dry powder inhalation device usually has a large volume and the manufacturing/purchasing cost is relatively high.
2) Dry Powder Inhalation Device with a Reservoir:
The representative of this type of dry powder inhalation device is commercially available product Turbuhaler.
A drug delivery device disclosed in a Chinese patent (Notice of Announcement No. CN 1054304C, Date of Announcement Jul. 12, 2000) comprises a powder vessel which can be filled with pulverized drug, and a measuring chamber connected with the powder vessel. The measuring chamber can separate the pulverized drug quantificationally from the vessel in batches.
An inhalation device disclosed in a Chinese patent (Notice of Announcement No. CN 1247275C, Date of Announcement Mar. 29, 2006) comprises a flow passage formed by a plurality of surfaces and a metering unit. The user's inspiration enables the airflow carrying with a dose of drug powder to pass through the flow passage; and the metering unit provides a dose of drug powder to the flow passage, so as to deliver the drug powder through the airflow.
It is clear that this type of dry powder inhalation device with a reservoir is usually equipped with a powder vessel and a corresponding metering component. The metering component separates the pulverized drug quantificationally from the powder cavern in batches.
A big problem of dry powder/micro powder administration is that the powder particles have high surface energy and are easy to form an agglomeration status, thus it is quite difficult to meter each dose of the storage drug.
Many attempts have been made to solve such a problem, for example, in Chinese patent ZL 91107979.3, a pressure is applied to the powder in the drug storage vessel via a spring. However, the force of the spring changes along with its length and the design flaw results in residual powder left in the device and/or leaking of powder; and also the mis-operation of over-dose can not be avoided.
However, since dry powder metering components in commercially available products and that disclosed in Chinese patent ZL 98805080.3, are through-holes, the leaking of powder occurs more frequently and the mis-operation of over-dose can not be avoided.
The drug measuring method in Chinese patent application 200780008580.7 also does not solve the problem of metering accurately when the dry powder is in a small quantity.
The international patent application with publication number of WO2008/001744 discloses a drug-dosing device with a vibration unit on the housing, which can produce vibration when the upper cover of the device is open. The purpose of setting this vibration unit is to make the drug powder to enter the measuring structure perfectly. However, it is difficult to judge how much contribution it makes to the drug powder to enter the measuring structure by vibrating the whole drug-dosing device.
Moreover, in commercially available dry powder inhalation devices with a reservoir, the air inlet/hole connected with the flow passage is usually equipped on the housing. When the protective cover of the dry powder device is removed, the air inlet is exposed in the air and the air channel connected with the powder vessel (air inlet/hole-flow passage-powder vessel-mouthpiece) is always in open status. The moisture in the air entered into the powder vessel makes the drug powder to be damp and caking easily and influences the accuracy of dosing and the use efficiency of the device.